Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens

Loïc Deblais, Yosra A. Helmy, Diapak Kathayat, Huang chi Huang, Sally A. Miller, Gireesh Rajashekara

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging chemical properties for antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were effective at 10 µM and higher against several serotypes, antibiotic-resistant, and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by altering cell membrane integrity. The four SMs displayed synergistic effects with ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were not pernicious to most eukaryotic cells at 200 μM and cleared internalized Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 µM and higher. The SMs also increased the longevity of Salmonella-infected Galleria mellonella larvae and reduced the population of internalized Salmonella Typhimurium. Two of the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca as well as its systemic translocation into other tissues, with minimal impact on the cecal microbiota. This study demonstrated that SMs are a viable source of potential antimicrobials applicable in food animal production against Salmonella.

Original languageEnglish
Article number13381
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Bibliographical note

Funding Information:
We thank Rosario A. Candelero for the technical support. We thank to Saranga Wijeratne and Dr. Tea Meulia, Molecular and Cellular Imaging Center, Ohio Agricultural Research and Development Center (http://oardc.osu. edu/mcic/), The Ohio State University for providing assistance with bioinformatics and microscopy analyses. The research in Dr. Rajashekara’s laboratory is supported by National Institute for Food and Agriculture (NIFA) Grant # 2013-67018-21240, U.S. Department of Agriculture.

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus subject areas

  • General

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